Our objective is to provide an unparalleled, centralized, publicly available resource with comprehensive, expertly annotated data, and analysis tools that informs design and interpretation of environmental health studies and promotes novel insights into the etiologies of environmentally influenced diseases. Most human diseases involve interactions between genetic and environmental factors. The environment is implicated in many common conditions such as asthma, cancer, and diabetes; however, the etiology of these widespread diseases remains unclear. More than 80,000 chemicals are currently used in commerce, challenging elucidation about chemical mechanisms of action and prioritization of environmental research. Integration of diverse data with novel analysis approaches is required to understand environment- disease associations and is essential for improving toxicity prediction, risk assessment, regulation and development of effective therapeutic interventions. We developed the Comparative Toxicogenomics Database (CTD; http://ctdbase.org) to enhance understanding about environment-disease connections by providing manually curated data describing chemical-gene interactions and chemical- and gene-disease relationships from the peer-reviewed literature and integrating these data with select external data sets (e.g., pathways and biological process data) and novel data analysis tools. Since its initial public release in 2004, CTD has become a well-established resource with a strong and expanding user base. This competitive renewal proposes to leverage and enhance the existing CTD framework, and continue our tradition of responding to the evolving needs of the environmental health research community by a) increasing the depth of content through comprehensive curation of our ?core? (chemical-gene/protein-disease) and exposure data, b) incorporating select public data sets to augment mechanism-based environmental health analyses, and c) developing and integrating novel analytical and visualization tools. These additions will significantly increase the impact of CTD on environmental health research by centralizing, harmonizing, and contextualizing information required to understand the complex relationships between diverse exposures and environmentally influenced diseases.